Olaparib (AZD2281) - Moligand™, 10mM in DMSO , PARP 1, 2 and 3 inhibitor, CAS No.763113-22-0, PARP 1, 2 and 3 inhibitor

CAS: 763113-22-0 Cat. No.: O408041 Peso molecular: 434.46 Número EC: 642-941-5

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

Ku-0059436

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

In vitro

Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50 >1 μM). Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. Olaparib is hypersensitive to BRCA1-deficient cell lines (MDA-MB-463 and HCC1937), compared with BRCA1- and BRCA2-proficient cell lines (Hs578T, MDA-MB-231, and T47D). Olaparib is strongly sensitive to KB2P cells due to suppression of base excision repair by PARP inhibition, which may result in the conversion of single-strand breaks to double-strand breaks during DNA replication, thus activating BRCA2-dependent recombination pathways.

In vivo

Combining with temozolomide, Olaparib (10 mg/kg, p.o.) significantly suppresses tumor growth in SW620 xenografts. Olaparib shows great response to Brca1^-/-;p53^-/- mammary tumors (50 mg/kg i.p. per day), while no responses to HR-deficient Ecad^-/-;p53^-/- mammary tumors. Olaparib even does not show dose-limiting toxicity in tumor-bearing mice. Olaparib has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, Olaparib shows selectively inhibition to ATM (Ataxia Telangiectasia Mutated)-deficient tumor cells, which indicates to be a potential agent for treating ATM mutant lymphoid tumors.
Cell Data

cell lines：Human leukemia cell lines including MV4;11, U937, Kasumi, MO7e, HL-60, TF-1, Jurkat, K562, THP-1, Hel 92.1.7; Solid tumor cell lines and HUVEC including PANC-1, HCT116, A549, HT-29, MCF7, PC-3, BXPC-3 and HUVEC

Concentrations：1-300 nM

Incubation Time：7-14 days

Powder Purity:≥99%

Specifications

Sinónimos

Ku-0059436

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM in cell-free assays, 300-times less effective against tankyrase-1. Olaparib induces significant autophagy that is associated with mitophagy in cells with BRCA mutatio

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

PARP 1, 2 and 3 inhibitor

Propiedades del producto

• ALogP: 1.9

Nombres e identificadores

• Isómeros SMILES: C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
• CAS alternativo: 763113-22-0
• Número NSC: 747856
• Términos de entrada MeSH: AZD 2281;AZD-2281;AZD221;AZD2281;Lynparza;olaparib
• Peso molecular: 434.46
• Reaxy-Rn: 12051534
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=12051534&ln=

Objetivos asociados (humanos)

TNKS Tchem Tankyrase-1 (1 Activities)

Discover Target: TNKS

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PARP4 Tchem Poly [ADP-ribose] polymerase 4 (2 Activities)

Discover Target: PARP4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PARP3 Tclin Poly [ADP-ribose] polymerase 3 (4 Activities)

Discover Target: PARP3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PARP1 Tclin Poly [ADP-ribose] polymerase 1 (60 Activities)

Discover Target: PARP1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PARP2 Tclin Poly [ADP-ribose] polymerase 2 (21 Activities)

Discover Target: PARP2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TNKS2 Tchem Tankyrase-2 (1 Activities)

Discover Target: TNKS2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro DMSO: 81 mg/mL (199.83 mM); Ethanol: 30 mg/mL (74.01 mM); Water: Insoluble

Referencias

1. Jingyan Yi, Xin Luo, Jinshan Xing, Aharon Gedanken, Xiukun Lin, Chunxiang Zhang, Gan Qiao.  (2023)  Micelle encapsulation zinc-doped copper oxide nanocomposites reverse Olaparib resistance in ovarian cancer by disrupting homologous recombination repair.  Bioengineering & Translational Medicine,  8  (3): (e10507).  [PMID:37206208] [10.1002/btm2.10507]

2. Teng Wang, Jiaojiao Tao, Bingjie Wang, Tianze Jiang, Xia Zhao, Yang Yu, Xin Meng.  (2023)  Reversing Resistance of Cancer Stem Cells and Enhancing Pdt Based on Hyaluronic Acid Nanomicelles for Preventing Cancer Recurrence and Metastasis.  Advanced Healthcare Materials,      [PMID:37941492] [10.1002/adhm.202302597]

3. Weimin Fang, Jinghao Wang, Xiaocong Ma, Ni Shao, Kunlin Ye, Dong Zhang, Changzheng Shi, Liangping Luo.  (2023)  A Progressively Disassembled DNA Repair Inhibitors Nanosystem for the Treatment of BRCA Wild-Type Triple-Negative Breast Cancer.  International Journal of Nanomedicine,      [PMID:37901361] [10.2147/IJN.S426639]

4. Teng Wang, Yang Yu, Bingjie Wang, Tianze Jiang, Xin Meng, Xia Zhao.  (2023)  Photothermal hyaluronic acid composite hydrogel targeting cancer stem cells for inhibiting recurrence and metastasis of breast cancer.  INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,      [PMID:37598824] [10.1016/j.ijbiomac.2023.126358]

5. Yang Yu, Teng Wang, Xin Meng, Tianze Jiang, Xia Zhao.  (2023)  Chitosan Thermosensitive Hydrogel Based on DNA Damage Repair Inhibition and Mild Photothermal Therapy for Enhanced Antitumor Treatment.  BIOMACROMOLECULES,      [PMID:37506051] [10.1021/acs.biomac.3c00430]

6. Huiling Zhou, Chenxin Duan, Huimin Qin, Chaonan Huang, Jingxuan Hou, Yanming Chen, Jin Zhu, Cangcang Xu, Jian Jin, Tao Zhuang.  (2023)  Synthesis and structural characterization of a novel palbociclib-kaempferol cocrystal with improved tabletability and synergistic antitumor activity.  JOURNAL OF MOLECULAR STRUCTURE,      [PMID:] [10.1016/j.molstruc.2023.135101]

7. Ren-Jiang Kong, Xin-Yu Li, Jia-Qi Huang, Xiang Zhou, Fu-An Deng, Yan-Mei Li, Ling-Shan Liu, Shi-Ying Li, Hong Cheng.  (2022)  A self-delivery photodynamic sensitizer for enhanced DNA damage by PARP inhibition.  Biomaterials Science,  11  (1): (162-169).  [PMID:36398488] [10.1039/D2BM01320G]

8. Chenxin Duan, Yanming Chen, Yuxin Zhang, Feifei Liang, Wenwen Liu, Xinyi Xiao, Cangcang Xu, Tao Zhuang, Chao Hao, Yin Chen.  (2022)  Two Cocrystals of Olaparib with Flavonoids toward Sustained Release: Structure, Dissolution Behavior, and Anticancer Activity Analysis.  CRYSTAL GROWTH & DESIGN,      [PMID:] [10.1021/acs.cgd.2c00370]

9. Huiping Hu, Yu Zhang, Wenting Ji, Hao Mei, Tingting Wu, Zihao He, Kaiping Wang, Chen Shi.  (2022)  Hyaluronic acid-coated and Olaparib-loaded PEI − PLGA nanoparticles for the targeted therapy of triple negative breast cancer.  JOURNAL OF MICROENCAPSULATION,      [PMID:34859741] [10.1080/02652048.2021.2014586]

10. Jiejie Sun, Jingzhou Liu, Chunhong Gao, Jinpeng Zheng, Jinbang Zhang, Yaning Ding, Wei Gong, Meiyan Yang, Zhiping Li, Yuli Wang, Yang Yang, Chunsheng Gao.  (2021)  Targeted delivery of PARP inhibitors to neuronal mitochondria via biomimetic engineered nanosystems in a mouse model of traumatic brain injury.  Acta Biomaterialia,      [PMID:34958970] [10.1016/j.actbio.2021.12.023]

11. Meng Ding, Lei Xu, Yumeng Zhang, Wei Li, Yuqing Zhao.  (2021)  Simultaneous quantification and ADME prediction of AD-1 and its eight metabolites in rat feces, and screening of PARP-1 inhibitors through molecular docking.  JOURNAL OF MOLECULAR STRUCTURE,      [PMID:] [10.1016/j.molstruc.2021.131016]

12. Yujie Peng, Meng Zhang, Libo Zhu, Wenqiang Qian, Jingjing Yan, Huidi Jiang, Yu Xin, Ying Zhang, Dongli Sun, Weidong Fei, Mengdan Zhao.  (2026)  Synergistic RU486 and olaparib therapy enhances apoptosis in endometriosis by simultaneously targeting hormonal signalling and DNA repair.  BRITISH JOURNAL OF PHARMACOLOGY,      [PMID:41707660] [10.1111/bph.70360]